Something goes wrong at an isolated scientific research station on Mars, run by the Union Aerospace Corporation (UAC). Communication from the station has failed with all research stopping. The only messages that are received from the station are more than slightly disturbing. Whatever happened caused the facility to undergo a level 5 quarantine, with the only souls allowed in or out being the Rapid Response Tactical Squad (RRTS). The RRTS is a team composed of hardened Space Marines armed to the teeth with enough firepower to neutralize any thread these soldiers come across. The research being done at Olduvai station has unwittingly opened a door, and all hell has broken loose. A legion of nightmarish creatures of unknown origin lurks behind every wall and stalks the countless rooms and tunnels of the facility, killing what few people remain. Sealing off the portal to Earth, Sarge (Dwayne "The Rock" Johnson), Reaper (Karl Urban) and their team must use every weapon at their disposal - and some they find along the way - to carry out their orders: nothing gets out alive.

The B.F.G. is a weapon that dates back to the game "Doom" back in 1993. There, it was the 'ultimate' weapon which, when fired, cleared the screen of foes in a great sickly green blast, consuming enormous amounts of ammo. It has showed up in various later games by both ID Software and third parties. Up to this movie, the acronym was never explained directly - although Sarge's version, "Big f**king gun" was for a long time the community's accepted name (also used in the original Doom design document, but not the game itself), and is most likely a homage to that.